WO1997003931A1 - Intrinsically labelled solid support - Google Patents
Intrinsically labelled solid support Download PDFInfo
- Publication number
- WO1997003931A1 WO1997003931A1 PCT/GB1996/001696 GB9601696W WO9703931A1 WO 1997003931 A1 WO1997003931 A1 WO 1997003931A1 GB 9601696 W GB9601696 W GB 9601696W WO 9703931 A1 WO9703931 A1 WO 9703931A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- compound library
- solid support
- supports
- synthesis
- reaction
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C40—COMBINATORIAL TECHNOLOGY
- C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
- C40B50/00—Methods of creating libraries, e.g. combinatorial synthesis
- C40B50/14—Solid phase synthesis, i.e. wherein one or more library building blocks are bound to a solid support during library creation; Particular methods of cleavage from the solid support
- C40B50/16—Solid phase synthesis, i.e. wherein one or more library building blocks are bound to a solid support during library creation; Particular methods of cleavage from the solid support involving encoding steps
-
- C—CHEMISTRY; METALLURGY
- C40—COMBINATORIAL TECHNOLOGY
- C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
- C40B20/00—Methods specially adapted for identifying library members
- C40B20/04—Identifying library members by means of a tag, label, or other readable or detectable entity associated with the library members, e.g. decoding processes
-
- C—CHEMISTRY; METALLURGY
- C40—COMBINATORIAL TECHNOLOGY
- C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
- C40B30/00—Methods of screening libraries
-
- C—CHEMISTRY; METALLURGY
- C40—COMBINATORIAL TECHNOLOGY
- C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
- C40B40/00—Libraries per se, e.g. arrays, mixtures
- C40B40/04—Libraries containing only organic compounds
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/58—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/11—Compounds covalently bound to a solid support
Definitions
- the present invention relates to compound libraries synthesised on solid supports provided with intrinsic labels, a method for the p., eduction of said compound libraries, a method for the characterisation of members of said compound hbraries which involves identifying the compounds by reference to the intrinsic labels of the associated solid supports and kits of intrinsically labelled solid supports for use in compound library synthesis.
- the individual components of the library may be tested either still attached to the polymer bead on which they were synthesised (Lam et al, Nature, 1991, 354, 82-84) or after cleavage from the bead (Salmon et al, Proc. Nat. Acad. Sci. USA, 1993, 11708-11712). If tested while attached to the bead, or cleaved but physically associated with the bead, it is necessary to devise a method of identifying the library compound which is bound to a bead found to be active in the test. Where this compound is a polypeptide identification may be achieved by Edman degradation, either directly or after cleavage from the bead (Lam et al, Bioorg. Med. Chem.
- oligonucleotides may be identified by microsequencing techniques (Dower et al, Ann. Rep. Med. Chem., 1991, 26, 271-280).
- researchers have attempted to identify peptides containing unnatural amino acids
- intrinsic labels has several advantages over prior art labelling methods including the possibility of manufacturing large quantities of intrinsically labelled supports prior to library synthesis thus increasing efficiency as no label has to be introduced concomitantly with the first reaction choice in the synthesis.
- intrinsic labels may be designed to be inert to a greater variety of synthetic conditions than pendant labels thus extending the range of chemistry which can be utilised in library synthesis.
- intrinsic labels avoid the possibility of a pendant label adversely affecting the test or of some co-operative interaction between the pendant label and the library compound resulting in false positive result.
- a compound library comprising a plurality of different units each comprising a solid support with which is associated a single member of the compound library, characterised in that each solid support has a defined chemical composition which acts as an intrinsic label capable of identifying the first reaction choice in the synthesis of the associated member of the compound library.
- the compound libraries according to the invention may comprise any convenient number of individual members, for example tens to hundreds to thousands to millions etc, of compounds.
- Suitable compounds include, for example, peptides, peptoids and other oligomeric compounds (cyclic or linear), and template-based smaller molecules, for example benzodiazepines, hydantoins, biaryls, polycyclic compounds (e.g. naphthalenes, phenothiazines, acridines, steroids etc), carbohydrate and amino acid derivatives, dihydropyridines, benzhydryls and heterocycles (e.g. triazines, indoles etc).
- the compound libraries preferably comprise chemical compounds of low molecular weight which have potential as therapeutic agents. Such compounds are for example of less than about 1000 daltons, such as less than 800, 600 or 400 daltons.
- any convenient solid support may be used provided that it is inert, that is to say its mechanical integrity and chemical composition is not affected by the rigours of library synthesis and testing to any relevant extent.
- the solid support may have any convenient structure and shape. Suitable solid supports include beads, pellets, discs, capillaries, hollow fibres, needles, solid fibres etc. Beads represent a particularly convenient solid support for use in compound library synthesis, such as combine/mix/divide processes.
- the beads may be made of any material having a rigid or semi-rigid surface such as cellulose, pore-glass, sihca gel, polystyrene resin, polystyrene cross-linked with divinyl benzene, grafted co-polymers such as polyethylene glycol/polystyrene, polyacrylamide, latex, dimethylacrylamide particularly cross-linked with N,N'-bis-acryloyl ethylene diamine and comprising N-t- butoxycarbonyl- ⁇ -alanyl-N'-acryloyl hexamethylene diamine.
- a rigid or semi-rigid surface such as cellulose, pore-glass, sihca gel, polystyrene resin, polystyrene cross-linked with divinyl benzene, grafted co-polymers such as polyethylene glycol/polystyrene, polyacrylamide, latex, dimethylacrylamide particularly cross-linked with N,N'-bis-acryloyl ethylene di
- the beads may also be composites such as glass particles coated with a hydrophobic polymer such as cross-linked polystyrene or a fluorinated ethylene polymer to which is grafted linear polystyrene.
- a hydrophobic polymer such as cross-linked polystyrene or a fluorinated ethylene polymer to which is grafted linear polystyrene.
- the solid support preferably comprises a polystyrene resin such as a polystyrene resin containing convenient reacting groups, e.g. amino, hydroxy or carboxy groups. Chloromethylpolystyrene resins such as chloromethylpolystyrene beads are a preferred sohd support.
- the inco ⁇ oration of the intrinsic label into the solid support is achieved by varying, in a controlled manner, the chemical composition of ⁇ e support during manufacture.
- the chemical composition of the support is preferably varied by the incorporation of quantities, for example up to 20% w/w, preferably 5-10% w/w, of at least one identifiable chemical compound into the material of the solid support.
- the identifiable chemical compounds are preferably distributed uniformly throughout the support. Suitable identifiable chemical compounds include substituted styrenes. Preferred styrenes include those with inert substituents such as halostyrenes, e.g. fluoro-, chloro, bromo- or iodostyrene, and protected hydroxystyrenes, e.g.
- chloromethylpolystyrene beads for example, containing intrinsic labels may be prepared by incorporating small amounts, for example up to 20% w/w, preferably 5- 10% w/w, of simple styrenes containing inert substituents into the mixture of chloromethyl- styrene, styrene and divinylbenzene commonly used for polymerisation to form beads for library synthesis.
- a large number of combinations and hence differently labelled sohd supports can be obtained using a relatively small number of substituted styrenes.
- a library is created, for example by the combine/mix/divide or split synthesis technique.
- Subsequent isolation of a solid support which has an associated library compound which exhibits a characteristic of interest, e.g. biological activity, followed by identification of the intrinsic label from the support allows identification of the portion of support used for the first stage of the synthesis and hence the nature of the first reaction choice, e.g.
- the first substituent introduced in the synthesis of the associated member of the compound library.
- Identification of the last reaction choice e.g. the last substituent introduced, by reference to the reaction which produced it, will also be possible if no 'mix' stage is performed. Knowing these two (first and last) reaction choices limits the number of possible structures for the member of the compound library to a level where it may be identified by, for example, mass spectrometry or iterative resynthesis.
- Synthesis of the compound libraries on the intrinsically labelled solid supports may comprise any convenient number of individual reaction steps.
- a method for the synthesis of a compound library comprising a plurality of different units each comprising a solid support with which is associated a single member of the compound library, which method comprises: a) apportioning solid supports among a plurality of reaction vessels such that each reaction vessel contains a portion of solid supports having a unique defined chemical composition which acts as an intrinsic label capable of identifying the first reaction choice in the synthesis of the associated member of the compound library; b) exposing the supports in each reaction vessel to a first reaction choice; c) pooling the supports; d) apportioning the supports among a plurality of reaction vessels; e) exposing the supports in each reaction vessel to a further reaction choice; and f) repeating steps c), d) and e) as required.
- the chemical composition of one portion of the solid support may be defined by the fact that it contains no additional labelling compounds other than that of the support material itself.
- the units comprising the compound libraries ofthe invention may also contain one or more inert secondary labels which are introduced during library synthesis by controlled chemical modification of the solid support. These secondary inert labels are capable of identifying an intermediate reaction choice in the synthesis of an associated member of the compound library.
- Particularly preferred intrinsic labels comprising latent groups are bromostyrene and iodostyrene.
- Preferred inert secondary inert labels include substituted monomers such as substituted styrenes produced by modification of latent groups on the intrinsic label.
- Suitable styrene substituents include vinyl, aryl e.g. phenyl, heterocyclyl and bicyclyl, and suostiiuted aryl e.g. substituted phenyl, heterocyclyl and bicyclyl.
- Suitable aryl substituents include chloro, fluoro, alkyl (C1-C4), alkoxy, trifiuoromethyl and mixtures of these, resulting in for example a (methylfluorophenyl)styrene label.
- Particular secondary labels which may be mentioned include 4-(4'-chlorophenyl)styrene, 4-(4'-trifluoromethyl-phenyl)styrene, 4-(4'- methoxyphenyl)styrene, 4-( 1 '-naphthyl)styrene.
- the particular chemistry which is used selectively to modify these latent groups and so introduce the secondary labels constitutes a further aspect of the invention.
- the inert secondary labels are conveniently introduced during library synthesis by, for example, such procedures as protecting group removal followed by acylation or alkylation.
- bromostyrene and/or iodostyrene particularly bromostyrene resins by a metal-catalysed cross-coupling reaction, e.g.
- a palladium-, nickel- or copper-catalysed cross-coupling reaction with an organometallic reagent, for example an arylboronate, organostannane, organozinc or organolithium reagent, in a so-called Heck, Stille or Suzuki coupling reaction (see for example Deshpande, Tetrahedron Lett., 1994, 35, 5613-4; Yu et al, Tetrahedron Utt., 1994, 35, 8919-22; Frenette & Friesen, Tetrahedron Lett., 1994, 35, 9177-80; and Forman & Sucholeiki, J. Org. Chem., 1995, 60, 523-8). If an equimolar mixture of two secondary labels is used then a large number of combinations is possible for a relatively small number of secondary labels.
- organometallic reagent for example an arylboronate, organostannane, organozinc or organolithium reagent
- the preferred synthesis of the secondary label is via a metal-catalysed cross-coupling reaction.
- Particularly preferred is the palladium-catalysed cross-coupling of an arylboronic acid to a latent group, in a so-called Suzuki couphng, where the intrinsic label is one of bromostyrene, iodostyrene or trifluoromethanesulphonyloxystyrene, the latter derived from protected hydroxy styrene.
- Chloromethylpolystyrene beads for example, containing intrinsic labels may be prepared by incorporating small amounts, for example up to 20% w/w, preferably 5-10%, of simple styrenes containing inert and latent substituents into the mixture of chloromethyl- styrene, styrene and divinylbenzene commonly used for polymerisation to form the resin beads for library synthesis. If an equimolar mixture of two styrenes containing inert substituents and one styrene containing a latent group is used then a large number of combinations and hence differently labelled solid supports can be obtained using a relatively small number of substituted styrene labels.
- libraj-y -.-. created, for example by the combine/mix/divide or split synthesis technique.
- Subsequent isolation of a solid support which has an associated compound which exhibits a characteristic of interest, e.g. biological activity, followed by identification of the intrinsic label from the support allows identification of the batch of support used for the first stage of the synthesis, and hence the nature of the first reaction choice, e.g. the first substituent introduced, in the synthesis of the associated member of the compound library.
- Identification of the secondary inert label(s) from the support allows the identification of the reaction choice from an intermediate round of the synthesis of the associated member of the compound library. Identification of the last reaction choice, e.g.
- a method for the characterisation of members of a compound library comprising a plurality of different units each comprising a sohd support with which is associated a single member of the compound library, which method comprises: i) synthesising the library by a method comprising: a) apportioning solid supports among a plurality of reaction vessels such that each reaction vessel contains a portion of solid support having a unique defined chemical composition which acts as an intrinsic label capable of identifying the first reaction choice in the synthesis of the associated member of the compound library; b) exposing the supports in each reaction vessel to a first reaction choice; c) pooling the supports; d) apportioning the supports among a plurality of reaction vessels; e) exposing the supports in each reaction vessel to a further reaction choice; and f) repeating steps c), d) and e) as required; ii) testing members of the compound library for a characteristic of interest; iii) selecting library compounds of interest; and iv)
- the test for the characteristic of interest may be a biological assay which tests the ability of library compounds to modulate, in a test system, the activity of a biological of interest.
- Convenient biologicals of interest include proteins such as enzymes, receptors, and the like. Suitable test systems will be apparent to the scientist of ordinary skill. Any convenient number of library compounds may be tested in the biological assay. The testing of the members of the compound library may be conducted whilst the compounds are still attached to the solid supports, alternatively the library compounds may be cleaved from the solid supports prior to testing.
- the intrinsic and optional inert secondary labels are conveniently excised from the resin by depolymerisation, for example thermal depolymerisation, prior to identification. They can then be identified by a technique such as mass spectrometry (ms) or gas chromatography (gc). A combined process such as gc/ms may also be used.
- depolymerisation for example thermal depolymerisation
- gc gas chromatography
- a single labelled polystyrene support is placed into the probe of a convenient mass spectrometer (for example magnetic sector, quadrupole, ion trap, or time of flight) and heated to a temperature of 500°C.
- a convenient mass spectrometer for example magnetic sector, quadrupole, ion trap, or time of flight
- spectra are obtained continuously and the decomposition of the polymer monitored by the total ion chromatograph and/or alternately the characteristic styrene monomer and dimer ions that constitute the bulk of the spectrum (m/z 77, 78, 91, 103, 104, 105, 115, 117, 118, 165, 178, 193, 207).
- the spectra are summed over the peak of the evolution profile to give one spectrum which is displayed over a limited mass range from 119 to 400.
- the label may then be identified by ions at the m/z corresponding to the mono-isotopic molecular weight ofthe compounds, e.g. substituted styrene monomers, that have been inco ⁇ orated into the support.
- the label comprises compounds which do not contain nitrogen then the ion at the m/z corresponding to the mono-isotopic molecular weight ofthe substituted styrene monomer will always possess an even mass number and its associated benzyl/tropylium ion 13 mass units (daltons) lower will thus always possess an odd mass number.
- the solid support may be divided into sections prior to chemical analysis, this can be accomplished by techniques such as milling, or preferably by microtomy.
- the latter technique can be performed at room temperature or at temperatures as low as -20°C to -70°C using a freezing microtome such as a Cryostat freezing microtome.
- a solid support associated with a library compound of interest is selected and mounted on or in a suitable support, for example a hard wax such as paraffin wax or beeswax; a resin such as polymethacrylate; a gum such as acacia; a suitable medium which can be frozen for use in a freezing microtome e.g.
- a handheld microtome, or other suitable microtome instrument for example a Cryostat can be used to pare, portion or slice the solid support into sections of suitable thickness. Sections of thickness less than about 200 microns, such as less than 100, 50, 10 or 5 microns are preferred.
- kits of intrinsically labelled solid supports such as labelled beads, as hereinbefore defined is novel.
- kits of solid supports for compound library synthesis compound library comprising a plurality of portions of a solid support upon which associated members of a compound library can be synthesised, characterised in that each portion of the solid support has a unique defined chemical composition which acts as an intrinsic label capable of identifying the first reaction choice in the synthesis of the associated member of the compound library.
- labelled supports are provided in sufficient quantity for use in the synthesis of compound libraries.
- Any convenient weight of material may be provided, such as for example up to 10, 100 or up to 1000 g of material. The maximum weight of material is limited only by practical considerations.
- Luperox 26 is hexaneperoxoic acid, 2-ethyl- 1,1 -dimethyl ethyl ester (CAS 3006-82-4). Luperox 26 is a trade mark of Elf Atochem.
- the product was filtered through a No. 2 sintered funnel using a water vacuum pump and washed with distilled water ( ⁇ 5 litres) to remove any inorganics and emulsion polymer formed.
- the product was washed with propan-2-ol (3 x 500 ml) stirring after each addition. It was then washed with THF (3 x 500 ml) stirring after each addition to swell the beads. The swollen beads were then washed with diethyl ether (3 x 500 ml).
- the product was transferred to a crystallising dish and shaken periodically to prevent the beads forming agglomerates whilst the ether evaporated. When dry the beads were placed in a vacuum oven at 60°C for -30 min to remove any remaining ether.
- Examples 2-5 illustrate the inco ⁇ oration of secondary labels into the intrinsically labelled solid supports.
- the inco ⁇ oration of the secondary label is illustrated without reference to library synthesis, however according to the invention the secondary labels would be introduced during library synthesis.
- Aqueous ammonia solution (5%, 0.5 ml) was added and the mixture stirred at room temperature for 20 min before the resin was removed by filtration and washed thoroughly with, in turn, DME, DME/5% ammonia (aq), DME, DME/0.2N HCl, DME, methanol, THF, methanol and ether, then dried under vacuum to give poly(4-(4'-trifluoromethyl- phenyl)styrene) (263 mg) with a conversion of approximately 70%. Found: C, 86.1%; H, 7.3%; N, 0%; Br, 2.7%.
- Example 4 Transformation of intrinsically-labelled poly(4-bromostyrene) into intrinsic/secondary-labelled poly(4-(4'-methoxyphenyl)styrene).
- poly(4-bromostyrene) 250 mg
- 4-methoxyphenylboronic acid 38 mg
- poly(4-(4'-methoxyphenyl)styrene) 157 mg
- poly(4-bromostyrene) 250 mg
- 1-naphthylboronic acid 43 mg
- poly(4-(l'naphthyl)styrene) 267 mg
- the trifluoromethylphenyl labelled resin showed the mono-isotopic molecular ion at m/z 248 for trifluoromethylphenylstyrene and the corresponding benzyl tropylium ion at m/z 235.
- a single resin bead containing chloromethylstyrene and fluorostyrene (as disclosed in Example 1) was also analysed. This showed the expected signature for fluorostyrene at m/z 122 and chloromethylstyrene at m/z 152(C135) and 154(C137) with the confirmatory ions at m/z 139 and 141.
Abstract
Description
Claims
Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP9506415A JPH11509542A (en) | 1995-07-22 | 1996-07-17 | Uniquely labeled solid support |
EP96924089A EP0843656A1 (en) | 1995-07-22 | 1996-07-17 | Intrinsically labelled solid support |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GBGB9515070.2A GB9515070D0 (en) | 1995-07-22 | 1995-07-22 | Label |
GB9515070.2 | 1995-07-22 |
Related Child Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US09/000,125 A-371-Of-International US20010007740A1 (en) | 1995-07-22 | 1996-07-17 | Intrinsically labelled solid support |
US10/339,552 Continuation US20030113805A1 (en) | 1995-07-22 | 2003-01-09 | Intrinsically labelled solid support |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1997003931A1 true WO1997003931A1 (en) | 1997-02-06 |
Family
ID=10778121
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/GB1996/001696 WO1997003931A1 (en) | 1995-07-22 | 1996-07-17 | Intrinsically labelled solid support |
Country Status (5)
Country | Link |
---|---|
US (2) | US20010007740A1 (en) |
EP (1) | EP0843656A1 (en) |
JP (1) | JPH11509542A (en) |
GB (1) | GB9515070D0 (en) |
WO (1) | WO1997003931A1 (en) |
Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1999035109A1 (en) * | 1998-01-05 | 1999-07-15 | Neogenesis, Inc. | Method for producing mass-coded combinatorial libraries |
EP1044364A1 (en) * | 1997-12-17 | 2000-10-18 | Aventis Pharmaceuticals Products Inc. | Method and reagents for the quantification of solid-phase reactions using fluorine nmr |
GB2349641A (en) * | 1998-07-02 | 2000-11-08 | Univ Hertfordshire | Use of coded particles in combinatorial chemistry |
US6694267B2 (en) | 1998-01-05 | 2004-02-17 | Neogenesis Drug Discovery, Inc. | Method for producing and screening mass-coded combinatorial libraries for drug discovery and target validation |
EP1728776A2 (en) * | 1998-01-05 | 2006-12-06 | Neogenesis, Inc. | Method for identifying a member of a mass-coded combinatorial library |
EP2354171A1 (en) * | 2010-02-02 | 2011-08-10 | Commissariat à l'Énergie Atomique et aux Énergies Alternatives | Fluorocarbonated polymer material and synthesis method |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103214677A (en) * | 2013-05-06 | 2013-07-24 | 曹曙光 | Alkali segmented copolymer polyelectrolyte with amphipathy and synthetic method thereof |
Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1992000091A1 (en) * | 1990-07-02 | 1992-01-09 | Bioligand, Inc. | Random bio-oligomer library, a method of synthesis thereof, and a method of use thereof |
WO1993006121A1 (en) * | 1991-09-18 | 1993-04-01 | Affymax Technologies N.V. | Method of synthesizing diverse collections of oligomers |
WO1993024517A2 (en) * | 1992-05-21 | 1993-12-09 | Furka Arpad | Peptide sub-library kits |
US5288514A (en) * | 1992-09-14 | 1994-02-22 | The Regents Of The University Of California | Solid phase and combinatorial synthesis of benzodiazepine compounds on a solid support |
WO1994008051A1 (en) * | 1992-10-01 | 1994-04-14 | The Trustees Of Columbia University In The City Of New York | Complex combinatorial chemical libraries encoded with tags |
WO1994013623A1 (en) * | 1992-12-11 | 1994-06-23 | Chiron Corporation | Synthesis of encoded polymers |
-
1995
- 1995-07-22 GB GBGB9515070.2A patent/GB9515070D0/en active Pending
-
1996
- 1996-07-17 WO PCT/GB1996/001696 patent/WO1997003931A1/en not_active Application Discontinuation
- 1996-07-17 US US09/000,125 patent/US20010007740A1/en not_active Abandoned
- 1996-07-17 JP JP9506415A patent/JPH11509542A/en active Pending
- 1996-07-17 EP EP96924089A patent/EP0843656A1/en not_active Ceased
-
2003
- 2003-01-09 US US10/339,552 patent/US20030113805A1/en not_active Abandoned
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1992000091A1 (en) * | 1990-07-02 | 1992-01-09 | Bioligand, Inc. | Random bio-oligomer library, a method of synthesis thereof, and a method of use thereof |
WO1993006121A1 (en) * | 1991-09-18 | 1993-04-01 | Affymax Technologies N.V. | Method of synthesizing diverse collections of oligomers |
WO1993024517A2 (en) * | 1992-05-21 | 1993-12-09 | Furka Arpad | Peptide sub-library kits |
US5288514A (en) * | 1992-09-14 | 1994-02-22 | The Regents Of The University Of California | Solid phase and combinatorial synthesis of benzodiazepine compounds on a solid support |
WO1994008051A1 (en) * | 1992-10-01 | 1994-04-14 | The Trustees Of Columbia University In The City Of New York | Complex combinatorial chemical libraries encoded with tags |
WO1994013623A1 (en) * | 1992-12-11 | 1994-06-23 | Chiron Corporation | Synthesis of encoded polymers |
Non-Patent Citations (1)
Title |
---|
F. W. FORMAN ET AL: "Solid Phase synthesis of Biaryls via the Stille Reaction", J. ORGANIC CHEMISTRY, vol. 60, 1995, pages 523 - 528, XP002006025 * |
Cited By (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1044364A4 (en) * | 1997-12-17 | 2004-10-06 | Aventis Pharm Prod Inc | Method and reagents for the quantification of solid-phase reactions using fluorine nmr |
EP1044364A1 (en) * | 1997-12-17 | 2000-10-18 | Aventis Pharmaceuticals Products Inc. | Method and reagents for the quantification of solid-phase reactions using fluorine nmr |
US6721665B2 (en) | 1998-01-05 | 2004-04-13 | Neogenesis Drug Discovery, Inc. | Method for producing and screening mass-coded combinatorial libraries for drug discovery and target validation |
US6207861B1 (en) | 1998-01-05 | 2001-03-27 | Neogenesis, Inc. | Method for producing and screening mass coded combinatorial libraries for drug discovery and target validation |
US6694267B2 (en) | 1998-01-05 | 2004-02-17 | Neogenesis Drug Discovery, Inc. | Method for producing and screening mass-coded combinatorial libraries for drug discovery and target validation |
US6714875B1 (en) | 1998-01-05 | 2004-03-30 | Neogenesis Drug Discovery, Inc. | Method for producing and screening mass-coded combinatorial libraries for drug discovery and target validation |
WO1999035109A1 (en) * | 1998-01-05 | 1999-07-15 | Neogenesis, Inc. | Method for producing mass-coded combinatorial libraries |
EP1728776A2 (en) * | 1998-01-05 | 2006-12-06 | Neogenesis, Inc. | Method for identifying a member of a mass-coded combinatorial library |
EP1728776A3 (en) * | 1998-01-05 | 2006-12-13 | Neogenesis, Inc. | Method for identifying a member of a mass-coded combinatorial library |
US7169563B2 (en) | 1998-01-05 | 2007-01-30 | Schering Corporation | Method for producing and screening mass-coded combinatorial libraries for drug discovery and target validation |
JP2011039067A (en) * | 1998-01-05 | 2011-02-24 | Neogenesis Inc | Manufacturing method of mass coded combinatorial library |
GB2349641A (en) * | 1998-07-02 | 2000-11-08 | Univ Hertfordshire | Use of coded particles in combinatorial chemistry |
EP2354171A1 (en) * | 2010-02-02 | 2011-08-10 | Commissariat à l'Énergie Atomique et aux Énergies Alternatives | Fluorocarbonated polymer material and synthesis method |
Also Published As
Publication number | Publication date |
---|---|
US20030113805A1 (en) | 2003-06-19 |
EP0843656A1 (en) | 1998-05-27 |
US20010007740A1 (en) | 2001-07-12 |
JPH11509542A (en) | 1999-08-24 |
GB9515070D0 (en) | 1995-09-20 |
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